Rapid cortisol signaling in response to acute stress involves changes in plasma membrane order in rainbow trout liver

Rapid cortisol signaling in response to acute stress involves changes in plasma membrane order in rainbow trout liver. Am J Physiol Endocrinol Metab 304: E1157-E1166, 2013. First published March 26, 2013; doi:10.1152/ajpendo.00500.2012.—The activation of genomic signaling in response to stressor-mediated cortisol elevation has been studied extensively in teleosts. However, very little is known about the rapid signaling events elicited by this steroid. We tested the hypothesis that cortisol modulates key stress-related signaling path- ways in response to an acute stressor in fish liver. To this end, we investigated the effect of an acute stressor on biophysical properties of plasma membrane and on stressor-related protein phosphorylation in rainbow trout (Oncorhynchus mykiss) liver. A role for cortisol in modulating the acute cellular stress response was ascertained by blocking the stressor-induced elevation of this steroid by metyrapone. The acute stressor exposure increased plasma cortisol levels and liver membrane fluidity (measured by anisotropy of 1,6-diphenyl-1,3,5- hexatriene), but these responses were abolished by metyrapone. Atomic force microscopy further confirmed biophysical alterations in liver plasma membrane in response to stress, including changes in membrane domain topography. The changes in membrane order did not correspond to any changes in membrane fatty acid components after stress, suggesting that changes in membrane structure may be associated with cortisol incorporation into the lipid bilayer. Plasma cortisol elevation poststress correlated positively with activation of intracellular stress signaling pathways, including increased phosphor- ylation of extracellular signal-related kinases as well as several puta- tive PKA and PKC but not Akt substrate proteins. Together, our results indicate that stressor-induced elevation of plasma cortisol level is associated with alterations in plasma membrane fluidity and rapid activation of stress-related signaling pathways in trout liver. fish; oncorhynchus mykiss; salmonid; glucocorticoid; stress response; membrane fluidity; cell signaling